Cyclopropanated macrocyclic ketones and lactones

ABSTRACT

The present invention is directed to novel cyclopropanated macrocyclic ketone and lactone compounds of the general formula 
     
       
         
         
             
             
         
       
         
         
           
             wherein X is an atom or a functional group selected from the group consisting of O, N, S, CH, or CH 2 ; 
             wherein Y is a straight or branched hydrocarbon moiety consisting of 1 to 20 carbon atoms; 
             wherein W is a straight or branched hydrocarbon moiety of consisting of 1 to 20 carbon atoms; and 
             wherein O is an oxygen atom;
 
and the use of these novel compounds in creating fragrances, and scents in items such as perfumes, colognes and personal care products.

FIELD OF THE INVENTION

The present invention relates to new chemical entities and the incorporation and use of the new chemical entities as fragrance materials.

BACKGROUND OF THE INVENTION

There is an ongoing need in the fragrance industry to provide new chemicals to give perfumers and other persons ability to create new fragrances for perfumes, colognes and personal care products. Those with skill in the art appreciate how differences in the chemical structure of the molecule can result in significant differences in the odor, notes and characteristics of a molecule. These variations and the ongoing need to discover and use the new chemicals in the development of new fragrances allows perfumers to apply the new compounds in creating new fragrances.

SUMMARY OF THE INVENTION

The present invention provides novel chemicals, and the use of the chemicals to enhance the fragrance of perfumes, toilet waters, colognes, personal products and the like. In addition, the present invention is directed to the use of the novel chemicals to enhance fragrance in perfumes, toilet waters, colognes, personal products and the like.

More specifically, the present invention is directed to the novel cyclopropanated macrocyclic compounds, represented by the general structure of Formula I set forth below:

-   -   wherein X is an atom or a functional group selected from the         group consisting of O, N, S, CH, or CH₂;     -   wherein Y is a hydrocarbon moiety consisting of 1 to 20 carbon         atoms and containing single and/or double bonds;     -   wherein W is a hydrocarbon moiety of consisting of 1 to 20         carbon atoms and containing single and/or double bonds;     -   wherein O is an oxygen atom.

Another embodiment of the invention is a method for enhancing a perfume by incorporating an olfactory acceptable amount of the compounds provided above.

Another embodiment of the invention is a method for enhancing a perfume by incorporating an olfactory acceptable amount of the compound of structure below:

These and other embodiments of the present invention will be apparent by reading the following specification.

DETAILED DESCRIPTION OF THE INVENTION

In Formula I above, Y and W represent straight or branched hydrocarbon moieties consisting of 1 to 20 carbon atoms and containing single and/or double bonds. Suitable straight hydrocarbon moieties include ethyl, propyl, butyl, pentyl, hexyl, and the like. Suitable branched hydrocarbon moieties include isopropyl, sec-butyl, tert-butyl, 2-ethyl-propyl, and the like. Suitable hydrocarbon moieties containing double bonds include ethene, propene, 1-butene, 2-butene, penta-1-3-deine, hepta-1,3,5-triene and the like.

In the preferred embodiment of the invention, the novel compounds of the present invention are represented by the following structures:

Those with the skill in the art will appreciate that the compound of Formula III is Bicyclo[13.1.0]hexadecan-4-one, the compound of Formula IV is 9-Oxa-bicyclo[15.1.0]octadecan-8-one, the compound of Formula V is Bicyclo[14.1.0]heptadecan-5-one, the compound of Formula VI is Bicyclo[15.1.0]octadecan-9-one and the compound of Formula VII is 5-Oxa-bicyclo[14.1.0]heptadecan-6-one, the compound of Formula VIII is 3-Methyl-bycyclo[13.1.0]hexadecane-5-one, the compound of Formula IX is Bicyclo[12.1.0]pentadecan-3-one, the compound of Formula X is 3-Methyl-6-oxa-bicyclo[13.1.0]hexadecane-7-one.

The table below lists additional compounds derived from Formula I that are described in the present invention:

W Y X Compound CH₂ (CH₂)₄ CH₂ Bicyclo[7.1.0]decan-3-one CH₂ (CH₂)₅ CH₂ Bicyclo[8.1.0]undecan-3-one (CH₂)₃ (CH₂)₅ CH₂ Bicyclo[10.1.0]tridecan-5-one (CH₂)₅ (CH₂)₅ CH₂ Bicyclo[12.1.0]pentadecan-7-one (CH₂)₅ (CH₂)₅ CH₂ Bicyclo[13.1.0]hexadecan-7-one CH₂ (CH₂)₅ O 4-Oxa-bicyclo[8.1.0]decan-3-one CH₂ (CH₂)₅ S 4-Thia-bicyclo[8.1.0]decan-3-one (CH₂)₅ (CH₂)₅ O 7-Oxa-bicyclo[12.1.0]pentadecan-8- one (CH₂)₅ (CH₂)₅ S 7-Thia-bicyclo[12.1.0]pentadecan-8- one (CH₂)₅ CH(CH₂)₄ CH Bicyclo[12.1.0]pentadec-8-en-7-one (CH₂)₉ C(CH₃)HCH₂ CH₂ 3-Methyl- bicyclo[13.1.0]hexadecane-5-one (CH₂)₉ C(CH₂CH₃)HCH₂ CH₂ 3-Ethyl-bicyclo[13.1.0]hexadecane- 5-one (CH₂)₉ C(CH₃)HCH₂ O 3-Methyl-4-oxa- bicyclo[13.1.0]hexadecane-5-one (CH₂)₉ C(CH₂CH₃)HCH₂ O 3-Ethyl-4-oxa- bicyclo[13.1.0]hexadecane-5-one (CH₂)₉ C(CH₃)HCH₂ S 3-Methyl-4-thia- bicyclo[13.1.0]hexadecane-5-one (CH₂)₉ C(CH₂CH₃)HCH₂ S 3-Ethyl-4-thia- bicyclo[13.1.0]hexadecane-5-one (CH₂)₉ C(CH₃)HCH₂ N 3-Methyl-4-aza- bicyclo[13.1.0]hexadecane-5-one (CH₂)₉ C(CH₂CH₃)HCH₂ N 3-Ethyl-4-aza- bicyclo[13.1.0]hexadecane-5-one (CH₂)₈CH(CH₃) (CH₂)₃ O 15-Methyl-5-oxa- bicyclo[14.1.0]heptadecan-6-one (CH₂)₈CH(CH₂CH₃) (CH₂)₃ O 15-Ethyl-5-oxa- bicyclo[14.1.0]heptadecan-6-one (CH₂)₆(CH)₂CH(CH₃) (CH₂)₃ O 15-Methyl-5-oxa- bicyclo[14.1.0]heptadec-13-en-6-one

The compounds of the present invention may be prepared from the corresponding alkenes, via Simmons-Smith cyclopropanation reaction. As described in the Examples below, compounds of Formulae III–X may be prepared via Simmons-Smith cyclopropanation reaction from the corresponding alkenes of the compounds below:

The alkenes of Formulae XI–XVIII are commercially available fragrance products. The compound of Formula XI is cyclopentadec-4-enone and is available from International Flavors & Fragrances Inc., New York, N.Y. under the trade name Musk Z4. The compound of Formula XII is oxacycloheptadec-9-en-2-one and is available from International Flavors & Fragrances Inc., New York, NY under the trade name Ambrettolide. The compound of Formula XIII is cyclohexadec-5-enone and is commercially available under the trade names Velvione and Ambretone. The compound of Formula XIV is cycloheptadec-9-enone is commercially available under the trade name Civettone. The compound of Formula XV is oxacyclohexadec-12-en-2-one. The compound of Formula XVI is 3-methyl-5-cyclopentadecene-1-one and is commercially available under the trade name of Muscenone. Preparation of 3-methyl-5-cyclopentadecene-1-one is described in U.S. Pat. No. 6,720,303. The compound of formula XVII is cyclotetradec-2-and or 3-ene-1-one and is available from the International Flavors & Fragrances Inc. The compound of Formula XVIII is 12-methyl-14-cyclotetradec-9-enolide, preparation of which is described in EP 908 455 A1.

Those with skill in the art will recognize that the compounds of the present invention have a number of chiral centers, thereby providing numerous isomers of the claimed compounds. It is intended herein that the compounds described herein include isomeric mixtures of such compounds, as well as those isomers that may be separated using techniques known to those having skill in the art. Suitable techniques include chromatography such as HPLC, and particularly gel chromatography and solid phase microextraction (“SPME”).

We have discovered that the compounds of Formulae III–X have a musk, sweet, floral tones that are well suited for use as a fragrance ingredient.

Another embodiment of the invention is a method for enhancing a perfume by incorporating an olfactory acceptable amount of the compound of structure below:

Preparation of the compound of Formula II is described in Eugene A. Mash et al., Journal of Organic Chemistry 61, page 2743, year 1996.

The use of the compounds of the present invention is widely applicable in current perfumery products, including the preparation of perfumes and colognes, the perfuming of personal care products such as soaps, shower gels, and hair care products as well as air fresheners and cosmetic preparations. The present invention can also be used to perfume cleaning agents, such as, but not limited to detergents, dishwashing materials, scrubbing compositions, window cleaners and the like.

In these preparations, the compounds of the present invention can be used alone or in combination with other perfuming compositions, solvents, adjuvants and the like. The nature and variety of the other ingredients that can also be employed are known to those with skill in the art.

Many types of fragrances can be employed in the present invention, the only limitation being the compatibility with the other components being employed. Suitable fragrances include but are not limited to fruits such as almond, apple, cherry, grape, pear, pineapple, orange, strawberry, raspberry; musk, flower scents such as lavender-like, rose-like, iris-like, carnation-like. Other pleasant scents include herbal and woodland scents derived from pine, spruce and other forest smells. Fragrances may also be derived from various oils, such as essential oils, or from plant materials such as peppermint, spearmint and the like.

A list of suitable fragrances is provided in U.S. Pat. No. 4,534,891, the contents of which are incorporated by reference as if set forth in its entirety. Another source of suitable fragrances is found in Perfumes, Cosmetics and Soaps, Second Edition, edited by W. A. Poucher, 1959. Among the fragrances provided in this treatise are acacia, cassie, chypre, cyclamen, fern, gardenia, hawthorn, heliotrope, honeysuckle, hyacinth, jasmine, lilac, lily, magnolia, mimosa, narcissus, freshly-cut hay, orange blossom, orchid, reseda, sweet pea, trefle, tuberose, vanilla, violet, wallflower, and the like.

Olfactory effective amount is understood to mean the amount of compound in perfume compositions the individual component will contribute to its particular olfactory characteristics, but the olfactory effect of the perfume composition will be the sum of the effects of each of the perftimes or fragrance ingredients. Thus the compounds of the invention can be used to alter the aroma characteristics of the perfume composition, or by modifying the olfactory reaction contributed by another ingredient in the composition. The amount will vary depending on many factors including other ingredients, their relative amounts and the effect that is desired.

The level of compound of the invention employed in the perfumed article varies from about 0.005 to about 10 weight percent, preferably from about 0.5 to about 8 and most preferably from about 1 to about 7 weight percent. In addition to the compounds other agents can be used in conjunction with the fragrance. Well known materials such as surfactants, emulsifiers, polymers to encapsulate the fragrance can also be employed without departing from the scope of the present invention.

Another method of reporting the level of the compounds of the invention in the perfumed composition, i.e., the compounds as a weight percentage of the materials added to impart the desired fragrance. The compounds of the invention can range widely from 0.005 to about 70 weight percent of the perfumed composition, preferably from about 0.1 to about 50 and most preferably from about 0.2 to about 25 weight percent. Those with skill in the art will be able to employ the desired level of the compounds of the invention to provide the desired fragrance and intensity.

The following are provided as specific embodiments of the present invention. Other modifications of this invention will be readily apparent to those skilled in the art. Such modifications are understood to be within the scope of this invention. As used herein all percentages are weight percent unless otherwise noted, ppm is understood to stand for parts per million and g is understood to be grams. IFF as used in the examples is understood to mean International Flavors & Fragrances Inc.

EXAMPLE A

Preparation of Bicyclo[13.1.0]hexadecan-4-one

To a dry 500 ml multi-neck round bottom flask fitted with an air stirrer, nitrogen inlet condenser and an addition funnel 2.7 g of 94% 4-cyclopentadecen-1-one and 50 ml of Methyl Tertiary Butyl Ether (MTBE) was added. The resulting mixture was stirred for 5 minutes. 21.8 ml of 1.1 M Et₂Zn were added slowly. The temperature of the mixture rose to 35° C. After the temperature of the mixture stabilized, 23 g of CH₂I₂ were added while stirring. The mixture was heated to 60° C. In about 60 minutes a first sample of the product was taken. The mixture was left to age overnight. Next morning, the mixture was quenched with saturated NH4Cl, aqueous layer separated and the organic layer washed with NaHCO₃.

The organic layer was then dried over anhydrous MgSO₄.

The gas chromatography test indicated that 74.4% of the starting alkene ketone converted to the cyclopropanated ketone.

The NMR spectrum of the Bicyclo[13.1.0]hexadecan-4-one is as follows: 0.6 ppm (m, 1H); 0.7 ppm (s, 2H); 0.9 ppm (m, 1H); 1.1 ppm (s, 1H); 1.2–1.4 ppm (m, 12H); 1.5 ppm (m, 5H); 1.7 ppm (m, 2H); 1.8 ppm (m, 1H); 2.1 ppm (s, 1H); 2.3–2.5 ppm (m, 3H); 3.6 ppm (m, 1H).

EXAMPLE B

Preparation of 9-Oxa -bicyclo[15.1.0]octadecan-8-one

To a dry 500 ml multi-neck round bottom flask fitted with an air stirrer, nitrogen inlet condenser and an addition funnel 8 g of ZnCu, 26 g of CH₂I₂, 100 ml of Et₂O and 2 crystals of I₂, were added and stirred. 12 g of oxacycloheptadec-8-en-2-one were added to the mixture and the mixture was heated to reflux. In 4 hours, first sample was taken at 35° C. The mixture was left to age overnight. Next morning, the mixture was quenched with saturated NH4Cl, aqueous layer separated and the organic layer washed with NaHCO₃. The organic layer was then dried over anhydrous MgSO₄.

The gas chromatography test indicated that 8.1% of the starting alkene lactone converted to the cyclopropanated lactone.

The NMR of 9-Oxa -bicyclo[15.1.0]octadecan-8-one is as follows: 0.0–0.2 ppm (m, 1H); 0.3 ppm (s, 1H); 0.4 ppm (s, 1H); 0.5 ppm (s, 1H); 0.8 ppm (m, 1H); 1.3 ppm (s, 14H); 1.6 ppm (m, 6H); 1.8 ppm (d, 1H); 2.0 ppm (m, 2H); 2.3 ppm (s, 2H); 4.1 ppm (m, 2H); 5.1 ppm (m, 1H).

EXAMPLE C

Preparation of Bicyclo[14.1.0]heptadecan-5-one

To a dry 500 ml multi-neck round bottom flask fitted with an air stirrer, nitrogen inlet condenser and an addition funnel 2.9 g of 5-cyclohexadecene-1-one and 25 ml of Methyl Tertiary Butyl Ether (MTBE) were added. 21.8 ml of 1.1 M solution of Et₂Zn in toluene was added via syringe while stirring. 23 g (6.9 ml) of CH₂I₂ was added all at once. The mixture was heated to 60° C. and the first sample was taken. The gas chromatography test indicated that 76.3% of the starting alkene ketone converted to the cyclopropanated ketone. 5 ml of Et₂Zn were added to the mixture and the mixture was stirred for 2 hours. A second sample was taken. The gas chromatography test indicated that 81.6% of the starting alkene ketone converted to the cyclopropanated ketone. Another 5 ml of Et₂Zn were added to the mixture and the mixture was stirred for 2 hours. A second third was taken. The gas chromatography test indicated that 83.6% of the starting alkene ketone converted to the cyclopropanated ketone. The mixture was left to age overnight. Next morning, the mixture was quenched with saturated NH₄Cl, aqueous layer separated and the organic layer washed with 200 ml of brine. The organic layer was then dried over anhydrous MgSO₄.

The NMR of the Bicyclo[14.1.0]heptadecan-5-one is as follows: 0.2 ppm (d, 2H); 0.4 ppm (s, 2H); 0.6 ppm (m, 11H); 0.7 ppm (s, 2H); 0.8 ppm (m, 1H); 1.1 ppm (m, 3H); 1.2–1.5 ppm (s, 39H); 1.6–1.8 ppm (m, 1H); 2.1 ppm (s, 3H); 2.2–2.7 ppm (m, 10H); 5.2–5.5 ppm (m, 2H).

EXAMPLE D

Preparation of Bicyclo[15.1.0]octadecan-9-one

To a dry 500 ml multi-neck round bottom flask fitted with an air stirrer, nitrogen inlet condenser and an addition funnel 3 g of 9-cycloheptadecene-1-one and 70 ml of Methyl

Tertiary Butyl Ether (MTBE) were added. 21.8 ml of 1.1 M solution of Et₂Zn in toluene was added via syringe while stirring. 23 g (6.9 ml) of CH₂I₂ was added all at once. The mixture was heated to 60° C. and the first sample was taken. The gas chromatography test indicated that 77.3% of the starting alkene ketone converted to the cyclopropanated ketone. The mixture was left to age overnight. Next morning, the mixture was quenched with saturated NH₄Cl, aqueous layer separated and the organic layer washed with 200 ml of brine. The organic layer was then dried over anhydrous MgSO₄.

The NMR of the Bicyclo[15.1.0]octadecan-9-one is as follows: 0.5 ppm (s, 1H); 0.6 ppm (s, 2H); 1.1 ppm (d, 2H); 1.3 ppm (s, 11H); 1.4 ppm (s, 8H); 1.6 ppm (s, 4H); 2.4 ppm (m, 4H).

EXAMPLE E

Preparation of 5-Oxa-bicyclo[14.1.0]heptadecan-6-one

To a dry 500 ml multi-neck round bottom flask fitted with an air stirrer, nitrogen inlet condenser and an addition funnel 16 g of ZnCu, 200 ml of Methyl Tertiary Butyl Ether (MTBE) were added and 3 crystals of I₂ were added and stirred. 104 g of CH₂I₂ was added while stirring. The mixture was heated maintained at 60° C. 48 g of oxacyclohexadec-12-en-2-one was added dropwise over 90 minutes. In another 20 minutes a first sample was taken. The gas chromatography test indicated that 45.9% of the starting alkene lactone converted to the cyclopropanated lactone at this point. In 2 hours a second sample was taken. The gas chromatography test indicated that 62.1% of the starting alkene lactone converted to the cyclopropanated lactone. The mixture was cooled to 30° C., quenched with saturated NH₄Cl, aqueous layer separated and the organic layer washed with 200 ml of brine. The organic layer was then dried over anhydrous MgSO₄.

The NMR of the 5-Oxa-bicyclo[14.1.0]heptadecan-6-one is as follows: 0.2 ppm (m, 1H); 0.3 ppm (m, 1H); 0.4 ppm (m, 2H); 0.6–0.8 ppm (d, 1H); 1.2–1.5 ppm (d, 13H); 1.7 ppm (s, 3H); 1.8 ppm (m, 2H); 2.1 ppm (s, 1H); 2.3–2.5 ppm (m, 2H); 4.0 4.1 ppm (m, 1H); 4.3 ppm (m, 1H).

EXAMPLE F

Preparation of 3-Methyl-6-oxa-bicyclo[13.1.0]hexadecane-7-one

To a dry 200 ml multi-neck round bottom flask fitted with an air stirrer, nitrogen inlet condenser and an addition funnel 2.9 g of 99% 3-Methyl-cyclopentadec-5-enone and 25 ml of Methyl Tertiary Butyl Ether (MTBE) was added. The resulting mixture was stirred for 5 minutes. 21.8 ml of 1.1 M Et₂Zn were added via syringe. After the temperature of the mixture stabilized, 23 g of CH₂I₂ were added while stirring. In about 60 minutes a first sample of the product was taken. The gas chromatography test indicated that 39.3% of the starting alkene lactone converted to the cyclopropanated lactone. The mixture was left to age overnight. Next morning, the mixture was quenched with saturated NH₄Cl, aqueous layer separated and the organic layer washed with NaHCO₃. The organic layer was then dried over anhydrous MgSO₄.

The gas chromatography test indicated that 39.3% of the starting alkene ketone converted to the cyclopropanated ketone.

The NMR spectrum of the 3-Methyl-6-oxa-bicyclo[13.1.0]hexadecane-7-one is as follows: 0.6 ppm (m, 2H); 0.8 ppm (s, 1H); 0.9 ppm (m, 1H); 1.1 ppm (m, 3H); 1.2–1.4 ppm (m, 11H); 1.7 ppm (m, 1H); 2.1 ppm (s, 1H); 2.2–2.4 ppm (m, 2H); 2.5 ppm (m, 1H).

Incorporation of Bicyclo[13.1.0]hexadecan-4-one into a ragrance formulation

Name Parts ALLYL CAPROATE 0.50 BENZYL ACETATE 130.00 CITRAL 0.50 CITRONELLOL 50.00 CITRONELLYL ACETATE 110.00 COUMARIN 11.00 BICYCLO[13.1.0]HEXADECAN-4-ONE 16.00 DAMASCENONE 1.00 ETHYL CAPROATE 1.00 ETHYL-2-METHYL BUTYRATE 1.00 GERANIOL 65.00 HEXENYL ACETATE, CIS-3 15.00 HEXYL ACETATE 2.25 IONONE ALPHA 12.00 IONONE BETA 12.00 ISO AMYL ACETATE 0.25 LINALOOL 45.00 LINALYL ACETATE 130.00 LYRAL 30.00 MANDARIN OIL MD REF A LMR 12.50 METHYL ANTHRANILATE 30.00 MUSKALACTONE 25.00 NONADIENAL, TRANS-2-CIS-6 15.00 ORANGE OIL BITTER WI 12.50 ORANGE OIL SWEET 25.00 PETITGRAIN 45.00 PHENYL ACETALDEHYDE 2.00 PHENYL ETHYL ALCOHOL 100.00 TAGETTE OIL EGYPT MD REF A LMR 7.50 TERPINEOL 80.00 UNDECALACTONE GAMMA 1.00 VETIVERT OIL HAITI MD REF A LMR 12.00 Total 1000.00

Name Parts ALLYL AMYL GLYCOLATE 1.00 BENZYL ACETATE 10.00 BENZYL SALICYLATE 55.00 BERGAMOT OIL 35.00 CASHMERAN 4.00 CEDRENYL ACETATE 20.00 CITRONELLOL 50.00 COUMARIN 25.00 CYCLOGALBANIFF 3.00 9-OXA-BICYCLO[15.1.0]OCTADECAN-8-ONE 7.50 DAMASCONE, DELTA 0.40 ETHYL VANILLIN 1.00 EUGENOL 40.00 GALAXOLIDE 90.00 GALBANUM OIL REF A LMR 0.10 GERANIOL 13.00 HEDIONE 80.00 HELIONAL 6.00 HELIOTROPINE 20.00 HEXENYL SALICYLATE, CIS-3 13.00 IONONE BETA 10.00 ISO E SUPER 60.00 JASMIN ABS EGYPT LMR 5.00 LILIAL 40.00 LINALOOL 80.00 LINALYL ACETATE 65.00 LYRAL 40.00 METHYL ANTHRANILATE 8.00 METHYL IONONE GAMMA 55.00 MUSKALACTONE 25.00 OLIBANUM COEUR DEP 50 PCT 6.00 PATCHOULI OIL 35.00 SANDALORE 20.00 SANJINOL 20.00 STYRALYL ACETATE 10.00 VANILLIN 13.00 VERAMOSS 4.00 VERTOFIX 25.00 YLANG OIL 5.00 Total 1000.00 

1. A compound Bicyclo[13.1.0]hexadecan-4-one. 